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| Content Provider | Springer Nature Link |
|---|---|
| Author | Ren, Biao Dai, Huan Qin Pei, Gang Tong, Yao Jun Zhuo, Ying Yang, Na Su, Meng Yi Huang, Pei Yang, Yu Zhuo Zhang, Li Xin |
| Copyright Year | 2014 |
| Abstract | Most screening approaches produce compounds that target survival genes and are likely to generate resistance over time. Simply having more drugs does not address the potential emergence of resistance caused by target mutation, drug efflux pumps over-expression, and so on. There is a great need to explore new strategies to treat fungal infections caused by drug-resistant pathogens. In this study, we found that azole-resistant Candida albicans with CaCDR1 and CaCDR2 over-expression is hypersensitive against amphotericin B (AmB) by our high throughput synergy screening (HTSS). In contrast, Δcdr1 and Δcdr2 knockout strains were resistant to AmB. Moreover, clinical isolates with increased expression of CaCDR1 and CaCDR2 demonstrated susceptibility to AmB, which can also synergize with the efflux pumps inducer fluphenazine (FPZ). Finally, the increased drug susceptibility to AmB in azole-resistant C. albicans with drug efflux pumps over-expression was consistent with the elevated expression of CaERG11 and its associated ergosterols in clinical isolates. Our data implies that the level of ergosterol contents determines the susceptibility to azoles and AmB in C. albicans. Deep understanding of the above mechanisms would offer new hope to treat drug-resistant C. albicans. |
| Starting Page | 2609 |
| Ending Page | 2616 |
| Page Count | 8 |
| File Format | |
| ISSN | 01757598 |
| Journal | Applied Microbiology and Biotechnology |
| Volume Number | 98 |
| Issue Number | 6 |
| e-ISSN | 14320614 |
| Language | English |
| Publisher | Springer Berlin Heidelberg |
| Publisher Date | 2014-01-17 |
| Publisher Place | Berlin, Heidelberg |
| Access Restriction | Subscribed |
| Subject Keyword | Drug resistance Amphotericin B Ergosterol Azoles Fluphenazine Microbiology Microbial Genetics and Genomics Biotechnology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Medicine Applied Microbiology and Biotechnology Biotechnology |
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